Research framework: Synucleinopathies are complex neurodegenerative disorders presenting with parkinsonism and the accumulation of pathologically altered alpha-synuclein in neuronal and glial cells. Synucleinopaties include Lewy body disorders (Parkinson’s disease, dementia with Lewy bodies), and multiple system atrophy. Pure autonomic failure and isolated REM-sleep behavior disorder are recognized among the premotor synucleinopathies leading to Lewy body disorders or multiple system atrophy. Disease-modifying therapies for synucleinopathies are lacking and current efforts to identify successful treatment for these disorders are limited due to frequent misdiagnosis in early stages and insufficient understanding of pathogenic factors.
Hypotheses: Our general hypothesis is that early events in synucleinopathies trigger cell-specific pathologies and define a set of prodromal signs that may serve as biomarkers of early diagnosis and disease progression. Understanding these highly dynamic events will lead to identification of disease targets and recognition of prodromal stages, facilitating disease-modifying therapies with higher chances of success.
Approach: Given the complexity of these diseases, TReND will employ a multidisciplinary approach based on a coordinated translational effort involving multiple PIs at different career stages and across different disciplines. The research projects combine experimental approaches, clinical data and assessments, body fluid, tissue, and neuroimaging biomarkers, and machine learning methods for their specific research aims.